A phase II open label clinical study of the safety, tolerability and efficacy of ILB® for Amyotrophic Lateral Sclerosis

Ann Logan; Zsuzsanna Nagy; Nicholas M Barnes; Antonio Belli; Valentina Di Pietro; Barbara Tavazzi; Giuseppe Lazzarino; Giacomo Lazzarino; Lars Bruce; Lennart I Persson

doi:10.1371/journal.pone.0267183

A phase II open label clinical study of the safety, tolerability and efficacy of ILB® for Amyotrophic Lateral Sclerosis

PLoS One. 2022 May 25;17(5):e0267183. doi: 10.1371/journal.pone.0267183. eCollection 2022.

Authors

Affiliations

¹ Axolotl Consulting Ltd, Droitwich, United Kingdom.
² Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
³ College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
⁴ Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of Rome, Rome, Italy.
⁵ Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁶ Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, Catania, Italy.
⁷ UniCamillus, Saint Camillus International University of Health Sciences, Rome, Italy.
⁸ Tikomed AB, Viken, Sweden.
⁹ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Abstract

Introduction: Amyotrophic lateral sclerosis (ALS) is an invariably lethal progressive disease, causing degeneration of neurons and muscle. No current treatment halts or reverses disease advance. This single arm, open label, clinical trial in patients with ALS investigated the safety and tolerability of a novel modified low molecular weight dextran sulphate (LMW-DS, named ILB®) previously proven safe for use in healthy volunteers and shown to exert potent neurotrophic effects in pre-clinical studies. Secondary endpoints relate to efficacy and exploratory biomarkers.

Methods: Thirteen patients with ALS were treated with 5 weekly subcutaneous injections of ILB®. Safety and efficacy outcome measures were recorded weekly during treatment and at regular intervals for a further 70 days. Functional and laboratory biomarkers were assessed before, during and after treatment.

Results: No deaths, serious adverse events or participant withdrawals occurred during or after ILB® treatment and no significant drug-related changes in blood safety markers were evident, demonstrating safety and tolerability of the drug in this cohort of patients with ALS. The PK of ILB® in patients with ALS was similar to that seen in healthy controls. The ILB® injection elicited a transient elevation of plasma Hepatocyte Growth Factor, a neurotrophic and myogenic growth factor. Following the ILB® injections patients reported increased vitality, decreased spasticity and increased mobility. The ALSFRS-R rating improved from 36.31 ± 6.66 to 38.77 ± 6.44 and the Norris rating also improved from 70.61 ± 13.91 to 77.85 ± 14.24 by Day 36. The improvement of functions was associated with a decrease in muscle atrophy biomarkers. These therapeutic benefits decreased 3-4 weeks after the last dosage.

Conclusions: This pilot clinical study demonstrates safety and tolerability of ILB® in patients with ALS. The exploratory biomarker and functional measures must be cautiously interpreted but suggest clinical benefit and have a bearing on the mechanism of action of ILB®. The results support the drug's potential as the first disease modifying treatment for patients with ALS.

Trial registration: EudraCT 2017-005065-47.

Publication types

Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Amyotrophic Lateral Sclerosis*
Biomarkers
Cohort Studies
Humans
Outcome Assessment, Health Care

Substances

Biomarkers

Associated data

EudraCT/2017-005065-47

Grants and funding

This study at the Sahlgrenska Hospital, Gothenburg, was funded by Tikomed AB (https://www.tikomed.com/) via the Clinical Trials Centre (https://www.gothiaforum.com/ctc). Tikomed AB and/or from Axolotl Consulting Ltd. provided support in the form of consultancy payments for LB, AL, NMB and ZN. The specific roles of these authors are articulated in the ‘author contributions’ section. Tikomed AB gave permission for publication and reviewed the manuscript prior to publication, but the funder had no additional role in the study design, data collection, and analysis.